The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis

This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.Universidade Federal do Paraná Departamento de Farmacologia Laboratório de Fisiologia e Farmacologia do Sistema Nervoso CentralUniversity of Hawaii Department of NeurobiologyUniversity of Hawaii Department of PsychologyUniversidade de São Paulo Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Departamento de PsicobiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de FisiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de NeuropsiquiatriaUniversidade Federal de Santa Catarina Departamento de FarmacologiaCentral Nervous System Research Department Sanofi SynthelaboAston University Institute of Pharmaceutical SciencesHoffmann-La Roche Ltd.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicologiaUniversity of Leeds Department of Psychology Ethopharmacology LaboratoryUniversidade Federal do Espírito Santo Centro de Biomedicina Departamento de Ciências FisiológicasUNIFESP, EPM, Depto. de PsicologiaSciEL

Anxiolytic-like effects of acute and chronic treatment with Achillea millefolium L. extract

AbstractEthnopharmacological relevanceAchillea millefolium L. (Asteraceae), known as yarrow (“mil folhas”), has been used as folk medicine for gastrointestinal disorders, inflammation, anxiety, and insomnia.AimTo evaluate the potential anxiolytic-like effect of hydroalcoholic extract of Achillea millefolium L. in animal models.MethodsThe present study evaluated the effects of the hydroalcoholic extract from the aerial parts of Achillea millefolium L. in mice subjected to the elevated plus-maze, marble-burying, and open-field tests. Additionally, the GABAA/benzodiazepine (BDZ) mediation of the effects of Achillea millefolium was evaluated by pretreatment with the noncompetitive GABAA receptor antagonist picrotoxin and the BDZ antagonist flumazenil and by [3H]-flunitrazepam binding to the BDZ site on the GABAA receptor.ResultsAchillea millefolium exerted anxiolytic-like effects in the elevated plus-maze and marble-burying test after acute and chronic (25 days) administration at doses that did not alter locomotor activity. This behavioral profile was similar to diazepam. The effects of Achillea millefolium in the elevated plus-maze were not altered by picrotoxin pretreatment but were partially blocked by flumazenil. Furthermore, Achillea millefolium did not induce any changes in [3H]-flunitrazepam binding.ConclusionThe results indicate that the orally administered hydroalcoholic extract of Achillea millefolium L. exerted anxiolytic-like effects that likely were not mediated by GABAA/BDZ neurotransmission and did not present tolerance after short-term, repeated administration

Efeito da corticosterona em ratos submetidos ao labirinto em cruz elevado e a convulsões induzidas pelo pentilenotetrazol

BV UNIFESP: Teses e dissertaçõe

EVIDENCE AGAINST THE INVOLVEMENT OF ACTH CRF RELEASE OR CORTICOSTEROID RECEPTORS IN THE ANXIOLYTIC EFFECT OF CORTICOSTERONE

The present study was designed to evaluate the role of ACTH and/or CRF release and corticosteroid receptors (glucocorticoid and mineralocorticoid) in the anxiolytic effect of corticosterone (CORT). Costicosteroid receptor mediation was evaluated using a dose-response analysis of the effect of CORT and by the action of dexamethasone (DEX), which binds to glucocorticoid receptors but not to mineralocorticoid receptors. DEX administration also permits indirect evaluation of the effect of ACTH/CRF release on the anxiolytic effect of CORT. Male Wistar rats (3 months old) weighing 250-350 g were treated sc with vehicle (N = 38), CORT 1.25 (N = 18), 2.5 (N = 13) and 5.0 (N = 24) mg/kg, or DEX 5.0 (N = 19) and 10.0 (N = 17) mg/kg and tested in the elevated plus-maze 2 h later. The group that received the highest dose of CORT (5.0 mg/kg) showed a significant increase in percent open arm entries (38 +/- 2.6, mean +/- SEM) as well as in percent time spent in open arms (27 +/- 4.0) when compared with the vehicle-treated rats (24.3 +/- 2.8 and 12.4 +/- 1.9, respectively; both P<0.05). There were no other significant differences among groups in the two parameters tested or in total arm entries. These data corroborate previous findings of the anxiolytic effect of CORT and suggest that inhibition of ACTH/CRF release and corticosteroid receptors do not play a major role in the anxiolytic effect of CORT.ESCOLA PAULISTA MED,DEPT PSICOBIOL,RUA BOTUCATU 862,1 ANDAR,BR-04023062 SAO PAULO,SP,BRAZILESCOLA PAULISTA MED,DEPT PSICOBIOL,RUA BOTUCATU 862,1 ANDAR,BR-04023062 SAO PAULO,SP,BRAZILWeb of Scienc

The Stroop color-word test recorded as a model of experimentally-induced anxiety

A corroboracao de um provavel efeito ansiolitico de uma droga psicotropica e obtida atraves de estudos controlados (randomizado, duplo-cego, comparativo com placebo) com pacientes com transtorno de ansiedade. Entretanto, o emprego de procedimentos em laboratorio que eliciem aumento da ansiedade em voluntarios normais e uma estrategia util tanto para avaliacao inicial de uma nova droga como para o estudo dos mecanismos psicobiologicos da ansiedade e dos transtornos de ansiedade. Estes modelos de ansiedade induzida experimentalmente apresentam como vantagens: rapidez de execucao, facilidade de recrutamento de voluntarios, maior controle e pureza da ansiedade, assim como dos possiveis efeitos colaterais. O teste de cor-palavra de Stroop tem sido empregado com esta finalidade. Entretanto, tem-se observado algumas dificuldades com sua utilizacao, entre elas uma inconsistencia na resposta ansiogenica ao teste. Determinou-se que a execucao do teste com limitacao do tempo e sinalizacao de erros foi eficaz em eliciar aumento de ansiedade estado somente em voluntarios com grau alto de ansiedade traco. Contudo, esta populacao, composta dos chamados 'voluntarios sintomaticos (que corresponde a pequena parcela dos voluntarios), ja apresentam valores elevados de ansiedade estado e a simples administracao de drogas ansioliticas acarreta reducoes significativas nesses valores. Por outro lado, a simulacao de falar em publico tem sido bastante empregada como metodo de inducao de ansiedade. Entretanto, alem de alguns resultados negativos com drogas ansioiiticas, nao existe uma boa padronizacao (p.ex. do topico a ser selecionado). Portanto, o objetivo do presente estudo foi o de avaliar a influencia da simulacao da execucao publica do SCWT (SCWT filmado) nos valores de ansiedade estado de voluntarios com grau medio de ansiedade traco. Tambem foram avaliados os possiveis fatores ansiogenicos do teste, bem como a resposta fisiologica (pulso, pressao arterial sistolica e diastolica e cortisol salivar) ao SCWT. Finalmente, desde que um procedimento valido deve ser capaz de detectar o efeito ansiolitico de uma droga clinicamente eficaz, avaliou-se o efeito da administracao de diazepam (em comparacao com placebo) na resposta de ansiedade estado ao SCWT filmado. No Experimento I observou-se que o SCWT nao filmado nao foi capaz de provocar aumento nos valores de ansiedade estado de voluntarios com grau medio de ansiedade traco, enquanto que o ..(au)BV UNIFESP: Teses e dissertaçõe